U.S. patent number 6,626,857 [Application Number 09/856,135] was granted by the patent office on 2003-09-30 for extracorporeal circulation device and method for isolation temperature control method.
This patent grant is currently assigned to Nikkiso Co., Ltd., Tomio Ohta. Invention is credited to Yoshihiko Kinoshita, Tetsuya Miyatake, Tomoya Murakami, Tomio Ohta.
United States Patent |
6,626,857 |
Ohta , et al. |
September 30, 2003 |
Extracorporeal circulation device and method for isolation
temperature control method
Abstract
An extracorporeal circulation apparatus used for the selective
temperature controlling method in which a temperature of an object
is kept at a predetermined temperature, includes: (A) a fluid
replacement supply unit which quantitatively supplies a fluid
replacement of which temperature has been adjusted into a blood
vessel; (B) a blood concentration unit which quantitatively
withdraws blood diluted by the fluid replacement from a blood
vessel and concentrates the withdrawn diluted blood; and (C) a
blood supply unit which controls a temperature of the blood which
has been concentrated and quantitatively supplies the concentrated
blood into a blood vessel, the blood concentration unit comprising
a diluted blood temperature sensor which measures a temperature of
the withdrawn diluted blood, and the fluid replacement supply unit
including a means which controls a temperature of the fluid
replacement to be supplied based on a different extent between the
measured diluted blood temperature and the predetermined
temperature of the object.
Inventors: |
Ohta; Tomio (Tezukayama
1-chome, Abeno-ku, Osaka-shi, Osaka 545-0037, JP),
Miyatake; Tetsuya (Shizuoka, JP), Kinoshita;
Yoshihiko (Tokyo, JP), Murakami; Tomoya (Sapporo,
JP) |
Assignee: |
Ohta; Tomio (Osaka,
JP)
Nikkiso Co., Ltd. (Tokyo, JP)
|
Family
ID: |
18223127 |
Appl.
No.: |
09/856,135 |
Filed: |
July 23, 2001 |
PCT
Filed: |
November 18, 1999 |
PCT No.: |
PCT/JP99/06434 |
PCT
Pub. No.: |
WO00/30702 |
PCT
Pub. Date: |
June 02, 2000 |
Foreign Application Priority Data
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|
|
|
|
Nov 19, 1998 [JP] |
|
|
10-329596 |
|
Current U.S.
Class: |
604/6.13; 422/44;
604/4.01; 604/5.01; 604/6.09; 604/6.11 |
Current CPC
Class: |
A61M
1/3455 (20130101); A61M 1/369 (20130101); A61M
1/3441 (20130101); A61M 1/3458 (20140204); A61M
2230/207 (20130101) |
Current International
Class: |
A61M
1/36 (20060101); A61M 1/34 (20060101); A61M
037/00 (); A61M 001/36 () |
Field of
Search: |
;604/6.09,6.11,6.13,4.01,5.01,6.15 ;422/44-48
;210/742,767,645,646 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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01259871 |
|
Oct 1989 |
|
JP |
|
05168703 |
|
Jul 1993 |
|
JP |
|
05309132 |
|
Nov 1993 |
|
JP |
|
8-266619 |
|
Oct 1996 |
|
JP |
|
Other References
Zukai:Dennetsu-Kogaku no Manabikata (Translated Abstract
provided)(Illustration: How to learn heat transfer ngineering)
(1.sup.st ed. by N. Kitayama, published by Ohmsha (Tokyo) Jul. 20,
1989, pp 104-109). .
Profound Hypotension with Differential Cooling of the Brain in
Dogs, J. Neurosurgery, vol. 24, pp. 993-1001, (1966). .
Selective Cooling of Brain Using Profound Hemodilution in Dogs,
Neurosurgery, vol.. 31, No. 6, pp. 1049-1054 (12/92). .
U.S. patent application Ser. No. 09/187986, filed Nov. 9, 1998.
.
Selective Hypothermic Perfusion of Canine Brain, Neurosurgery, vol.
38, No. 6, p. 1211-1215..
|
Primary Examiner: Sykes; Angela D.
Assistant Examiner: Deak; Leslie R
Attorney, Agent or Firm: Darby & Darby
Claims
What is claimed is:
1. An extracorporeal circulation apparatus for a selective
temperature controlling method in which the temperature of an
object is kept at a predetermined temperature, comprising: (A) a
fluid replacement supply unit which quantitatively supplies a fluid
replacement into a blood vessel wherein said fluid replacement
supply unit comprises a means for controlling the temperature of
the fluid replacement based on a different extent between: (1) the
measured diluted blood temperature and (2) the predetermined
temperature of the object; (B) a blood concentration unit which
quantitatively withdraws blood diluted by the fluid replacement
from a blood vessel and concentrates the withdrawn diluted blood
wherein said blood concentration unit comprises: a diluted blood
temperature sensor which measures the temperature of the withdrawn
diluted blood; and a filtration means for separating out filtrate;
and (C) a blood supply unit which controls a temperature of the
blood which has been concentrated and quantitatively supplies the
concentrated blood into a blood vessel.
2. An extracorporeal circulation apparatus, according to claim 1,
wherein: the control of the temperature of the fluid replacement to
be supplied is carried out considering heat transfer between the
fluid replacement and a surrounding of the apparatus until the
fluid replacement of which temperature has been adjusted is
supplied into the blood vessel.
3. An extracorporeal circulation apparatus, according to claim 2,
wherein: the control of the means which controls the temperature of
the fluid replacement is carried out based on Equation (I):
4. An extracorporeal circulation apparatus, according to claim 1,
wherein: the supplied fluid replacement is injected into the blood
vessel through an artificial lung.
5. An extracorporeal circulation apparatus, according to claim 4,
further comprising, in place of the artificial lung, a drip chamber
into which oxygen is injected.
6. An extracorporeal circulation apparatus, according to claim 1,
wherein: a portion of the withdrawn diluted blood is injected into
the blood vessel together with the fluid replacement to be injected
after the withdrawn diluted blood passes through an artificial
lung.
7. An extracorporeal circulation apparatus, according to claim 1,
wherein: the fluid replacement supply unit supplies autologous
blood or transfusion blood together with the fluid replacement, and
the autologous blood or the transfusion blood is supplied through
an artificial lung together with the fluid replacement into the
blood vessel.
8. An extracorporeal circulation apparatus, according to claim 1,
wherein: a temperature of the supplied fluid replacement has been
adjusted to a temperature within a temperature range of 36.5 C. to
3 C. and the fluid replacement is used for the selective cooling
method.
9. An extracorporeal circulation apparatus, according to claim 1,
wherein: a temperature of the supplied fluid replacement has been
adjusted to a temperature within a temperature range of 36.5 C. to
42 C. and the fluid replacement is used for the selective warming
method.
10. An extracorporeal circulation apparatus, according to claim 1,
wherein: a flow rate of the injected fluid replacement Vd is 10 to
600 ml/min., preferably 50 to 500 ml/min., and more preferably 100
to 400 ml/min., and the blood concentration unit comprises a
filtration unit which is controlled such that a flow rate of
filtrate Vb is 10 to 200 ml/min., preferably 50 to 170 ml/min., and
more preferably 100 to 140 mil/min.
11. An extracorporeal circulation apparatus, according to claim 1,
wherein: the blood concentration unit concentrates the diluted
blood to a hematocrit value of at least 70% of that before being
diluted.
12. An extracorporeal circulation apparatus, according to claim 1,
further comprising: a means for controlling the flow rates of the
supplied fluid replacement, the withdrawn diluted blood, and the
filtrate.
13. An extracorporeal circulation apparatus, according to claim 1,
wherein: the blood concentration unit comprises a dialysis
device.
14. An extracorporeal circulation apparatus, according to claim 1,
wherein: the means which controls the temperature of the supplied
fluid replacement comprises a Peltier element.
15. An extracorporeal circulation apparatus, according to claim 1,
wherein: the selective temperature controlling method is a
selective cooling method or a selective warming method.
16. An extracorporeal circulation apparatus, according to claim 1,
wherein: the selective temperature controlling method is a
temperature recovery method after a selective cooling method or
after a selective warming method.
17. An extracorporeal circulation apparatus, according to claim 1,
wherein: the apparatus is used for a surgical operation.
18. An extracorporeal circulation apparatus, according to claim 1,
wherein: the apparatus is used for controlling a condition of a
part of a body.
19. An extracorporeal circulation apparatus for a selective
temperature controlling method in which the temperature of an
object is kept at a predetermined temperature, comprising: (A) a
fluid replacement supply unit which quantitatively supplies fluid
replacement into a blood vessel wherein: said fluid replacement
supply unit comprises a temperature sensor which measures the
temperature of the supplied fluid replacement; said fluid
replacement supply unit comprises a means for controlling the
temperature of the fluid replacement based on a different extent
between: (1) an averaged temperature of the measured supplied fluid
replacement temperature and the measured diluted blood temperature,
and (2) the predetermined temperature of the object; (B) a blood
concentration unit which quantitatively withdraws blood diluted by
the fluid replacement from a blood vessel and concentrates the
withdrawn diluted blood; wherein said blood concentration unit
comprises a diluted blood temperature sensor which measures the
temperature of the withdrawn diluted blood; and (C) a blood supply
unit which controls a temperature of the blood which has been
concentrated and quantitatively supplies the concentrated blood
into a blood vessel.
20. An extracorporeal circulation apparatus, according to claim 19,
wherein: the control of the temperature of the fluid replacement to
be supplied is carried out considering heat transfer between the
fluid replacement and a surrounding of the apparatus until the
fluid replacement of which temperature has been adjusted is
supplied into the blood vessel.
21. An extracorporeal circulation apparatus, according to claim 20,
wherein: the control of the means which controls the temperature of
the fluid replacement is carried out based on Equation (II):
22. An extracorporeal circulation apparatus, according to claim 19,
wherein: the supplied fluid replacement is injected into the blood
vessel through an artificial lung.
23. An extracorporeal circulation apparatus, according to claim 19,
wherein: the fluid replacement supply unit supplies autologous
blood or transfusion blood together with the fluid replacement, and
the autologous blood or the transfusion blood is supplied through
an artificial lung together with the fluid replacement into the
blood vessel.
24. An extracorporeal circulation apparatus, according to claim 19,
further comprising, in place of the artificial lung, a drip chamber
into which oxygen is injected.
25. An extracorporeal circulation apparatus, according to claim 19,
wherein: the fluid replacement supply unit comprises a catheter
through which the fluid replacement is injected, the supplied fluid
replacement temperature sensor is located at around a leading end
of the catheter on a distal side thereof, the blood concentration
unit comprises a catheter through which the diluted blood is
withdrawn and a diluted blood temperature sensor is located at
around a leading end of the catheter on a distal side thereof.
26. An extracorporeal circulation method for maintaining selective
temperature control to keep an object at a predetermined
temperature, which comprises the steps of: (A) quantitatively
supplying a fluid replacement of which temperature has been
adjusted into a blood vessel by means of a fluid replacement supply
unit; (B) controlling a temperature of the fluid replacement which
is quantitatively supplied by the fluid replacement supply unit
based on a different extent between: (1) the measured diluted blood
temperature and (2) the predetermined temperature of the object;
(C) quantitatively withdrawing blood diluted by the fluid
replacement from a blood vessel and concentrating the withdrawn
blood by means of a blood concentration unit; and (D) measuring a
temperature of the withdrawn diluted blood by means of the blood
concentration unit; and (E) controlling a temperature of the blood
which has been concentrated and quantitatively supplying the blood
into a blood vessel by a blood supply unit.
27. An extracorporeal circulation method, according to claim 26,
wherein controlling the temperature of the fluid replacement
comprises the step of compensating for heat transfer between the
fluid replacement and the atmosphere surrounding the apparatus
until the temperature controlled fluid replacement is supplied into
the blood vessel.
28. An extracorporeal circulation method, according to claim 26,
wherein: upon starting the method, a temperature of the fluid
replacement has been adjusted to the predetermined temperature of
the object.
29. An extracorporeal circulation method, according to claim 26,
wherein the method includes an extracorporeal circulation apparatus
comprising: (A) a fluid replacement supply unit which
quantitatively supplies a fluid replacement of which temperature
has been adjusted into a blood vessel; (B) a blood concentration
unit which quantitatively withdraws blood diluted by the fluid
replacement from a blood vessel and concentrates the withdrawn
diluted blood; and (C) a blood supply unit which controls a
temperature of the blood and which has been concentrated and
quantitatively supplies the concentrated blood into a blood vessel,
the blood concentration unit comprising a diluted blood temperature
sensor which measures a temperature of the withdrawn diluted blood,
and the fluid replacement supply unit comprising a means which
controls a temperature of the fluid replacement to be supplied
based on a different extend between the measured diluted blood
temperature and the predetermined temperature of the object.
30. An extracorporeal circulation method for maintaining selective
temperature control to keep an object at a predetermined
temperature, which comprises the steps of: (A) quantitatively
supplying a fluid replacement of which temperature has been
adjusted into a blood vessel by means of a fluid replacement supply
unit; (B) controlling a temperature of the fluid replacement which
is quantitatively supplied by the fluid replacement supply unit
based on a different extent between the measured diluted blood
temperature and the predetermined temperature of the object; (C)
measuring a temperature of the supplied fluid replacement by means
of the fluid replacement supply unit; and (D) controlling the
temperature of the supplied fluid replacement, by means of the
fluid replacement supply unit, based on a different extent between:
(1) an averaged temperature of the measured fluid replacement
temperature which is quantitatively supplied and the measured
diluted blood temperature, and (2) the predetermined temperature of
the object; (E) quantitatively withdrawing blood diluted by the
fluid replacement from a blood vessel and concentrating the
withdrawn blood by means of a blood concentration unit; (F)
measuring a temperature of the withdrawn diluted blood by means of
the blood concentration unit; and (G) controlling a temperature of
the blood which has been concentrated and quantitatively supplying
the blood into a blood vessel by a blood supply unit.
31. An extracorporeal circulation method, according to claim 30,
wherein controlling the temperature of the fluid replacement
comprises the step of compensating for heat transfer between the
fluid replacement and the atmosphere surrounding the apparatus
until the temperature controlled fluid replacement is supplied into
the blood vessel.
Description
TECHNICAL FIELD
The present invention relates to an extracorporeal circulation
apparatus used for various treatments in the medical field related
to a mammal and especially a human, and particularly to a novel
extracorporeal circulation apparatus which is usable for a case in
which a selected part of a body is to be kept at a predetermined
(or preset) temperature by the "selective temperature controlling
(or adjusting) method" such as the "selective cooling method" or
the "selective warming method." The apparatus of the present
invention will be explained hereinafter with an example in a case
of a human, but it is understood that the present invention is
applicable to any mammal.
BACKGROUND ART
Since Woodhall introduced in 1960 a systemic profound hypothermia
under a cardiac arrest for the purpose of protecting a brain
against a hemorrhage or an ischemia upon a craniotomy, the systemic
profound hypothermia has been employed in many types of operations.
However, a pump-oxygenator employed in this method makes the
procedure complicated and the blood perfusion to various organs
insufficient and the method requires a large amount of heparin as
an anticoagulant, resulting in problems such as a secondary
cerebral hemorrhage.
One of the inventors has made an effort to overcome the problems
mentioned above and has developed a method for cooling a brain
selectively (which is substantially the same in its meanings as the
abovmentioned "selective cooling method") while using a
pump-oxygenator, and applied the method to a craniotomy (see J.
Neurosurg; Vol 24, pages 993 to 1001, 1996). This selective cooling
method did provide a cerebral hypotension of the brain safely, but
still involved the problems with regard to the intra- and
post-operative hemorrhages due to the use of a large amount of
heparin still associated therewith.
In order to overcome these problems, one of the inventors
discovered a method for injecting a cooled lactated Ringer's
solution as a fluid replacement (or a replenisher liquid) into a
cerebral artery so as to cool only a brain exclusively and to
dilute a blood simultaneously while cooling the blood, resulting in
a substantially reduced heparin level, whereby reducing the risk of
the hemorrhage (see Neurosurgery; Vol 31, pages 0149 to 1054,
1992). This method allows a reversible extreme hypotension to be
established without undergoing an oxygen deficit and enables an
extreme reduction in the amount of heparin to be used as a result
of introduction of the cooled fluid replacement, whereby allowing
the amount of heparin to be close to that used in an ordinary
angiography. In addition, the introduction of the diluted blood
into a lesion leads to various safety-improving effects such as
reduction in blood loss.
As described above, since the brain temperature is lowered by
injecting the cooled lactated Ringer's solution. However, an amount
of the lactated Ringer's solution to be injected is generally
large, the injection of the lactated Ringer's solution dilutes the
blood excessively and an amount of circulating blood is increased
which results in the excessive body fluid condition, so that
keeping the low temperature condition for a long time becomes
difficult. Therefore, there is a problem in that a satisfactory low
blood pressure condition (or cerebral hypotension) of the brain is
not ensured. In addition to this, other problems may be occur: for
example a large amount of low temperature diluted blood fills the
body and a body temperature is lowered, a blood activity is
lowered, balancing electrolytes in the blood becomes required, and
an excessive overhydration condition may occur which cannot be
attended at all with a diuretic drug.
Thus, one of the inventors studied the above problems extensively
and proposed an extracorporeal circulation apparatus, which
comprises (1) a fluid replacement supply unit which cools a fluid
replacement (or a diluent or a replenisher liquid) and
quantitatively injects the fluid replacement into a blood vessel
(and thus into a body), (2) a blood concentration unit which
quantitatively withdraws blood diluted by the fluid replacement
from a blood vessel (and thus from the body) and concentrates the
withdrawn diluted blood, and (3) a blood supply unit which
quantitatively injects the concentrated blood into a blood vessel.
Details of this apparatus is disclosed in Japanese Patent Kokai
Publication No.9-290021. It is noted that the disclosure of the
Publication is incorporated herein by the reference thereto. Using
such extracorporeal circulation apparatus allows the selective
cooling method to be carried out effectively.
DISCLOSURE OF INVENTION
In order to carry out the selective cooling method more smoothly,
the present inventors have further studied the extracorporeal
circulation apparatus which has been already proposed as described
above, and have found that it is necessary for the more effective
selective cooling method to more precisely control a temperature of
an object which is a part of a body and to which the selective
cooling method is applied (or a region of the body such as an
organ, for example a brain, which is also referred to as merely
"object"), and that it is important for such precise temperature
control to measure a temperature of the diluted blood which is
withdrawn from the interior of the body and control a temperature
of the fluid replacement which is to be supplied into the interior
of the body based on the measured temperature of the diluted blood
when the extracorporeal circulation apparatus as described above is
used, whereby the inventors have completed the present invention.
That is, it has been found that the temperature of the object to
which the selective cooling method is applied is more precisely
controlled by measuring the temperature of the diluted blood which
is withdrawn from the inside of the body and controlling the
temperature of the fluid replacement which is to be supplied into
the inside of the body based on the measured temperature of the
diluted blood, whereby the selective cooling method is carried out
more effectively.
In addition, there is a case in which it is desirable to warm an
object to a predetermined temperature depending on a treatment for
the object (i.e. a case of a selective warming method), and it has
been found that when the object is, not cooled as described above,
but warmed, the object to which the selective warming method is
applied is more precisely controlled by controlling the temperature
of the fluid replacement which is to be supplied into the inside of
the body based on the measured temperature of the diluted blood,
whereby the selective warming method is carried out more
effectively.
That is, it has been found that when an selective temperature
controlling method is applied in which a temperature of an object
which is a part of a body is controlled to a predetermined
temperature depending on a treatment for the object, the
temperature of the object to which the selective temperature
controlling method is applied is more precisely controlled by
measuring the temperature of the diluted blood which is withdrawn
from the interior of the body and controlling (or adjusting) the
temperature of the fluid replacement which is to be supplied into
the interior of the body based on the measured temperature of the
diluted blood, whereby the selective temperature controlling method
is carried out more effectively. The application of the present
invention to the selective temperature controlling method will be
explained hereinafter with reference mainly to the selective
cooling method as an example. Since the selective warming method
can be generally carried out substantially similarly to the
selective cooling method except that the object is warmed in the
selective warming method, those skilled in the art would readily
apply the apparatus according to the present invention to the
selective warming method based on the example of the selective
cooling method.
It should be noted that in the extracorporeal circulation apparatus
of the prior art which can be applied to the selective cooling
method as described in Japanese Patent Kokai Publication No.
9-290021, the temperature measurement of the withdrawn diluted
blood is not considered at all. Further, the Publication suggests
that a temperature of a fluid replacement itself which is to be
supplied to the interior of the body is controlled to a preset
temperature by a heat exchanger through which the fluid replacement
is passed depending on a temperature to which the object is to be
cooled, but the temperature of the withdrawn diluted blood is not
considered at all as to the temperature control of the fluid
replacement. Such control of the prior art supplies the fluid
replacement which has been controlled to the temperature by the
heat exchanger beforehand irrespective of a condition of the object
to which the selective cooling method is being applied. However,
the condition of the object to which the selective cooling method
is applied may change momentarily, which results in that the
temperature of the object deviates from a predetermined temperature
at which the object is to be kept, so that the temperature of the
withdrawn diluted blood may change. For example, an organ as the
object swells up and its temperature rises, and thereby the
temperature of the withdrawn diluted blood may rise. In such case,
in order to decrease the temperature of the organ as the object to
the originally predetermined temperature so as to carry out the
selective cooling method, it is necessary to lower the temperature
of the fluid replacement to be supplied so as to suppress the
temperature increase of the organ itself, and vice versa.
However, since the extracorporeal circulation apparatus of the
prior art as described above does not take the temperature of the
withdrawn diluted blood into consideration, it cannot be adapted to
the condition change of the object of the selective cooling method,
and thus the change of the diluted blood temperature, whereby there
may be a problem in that the selective cooling method cannot be
applied properly. The present invention solves such a problem.
That is, the present inventors have found that by measuring the
temperature of the diluted blood which is withdrawn from the
interior of the body and controlling the temperature of the fluid
replacement which is to be supplied into the interior of the body
based on the measured temperature of the diluted blood, the
temperature control of the object to which the selective
temperature controlling method such as the selective cooling method
or the selective warming method is applied is carried out more
precisely, so that the selective temperature controlling method is
carried out more effectively.
It is noted that depending on a kind of the object to which the
selective temperature controlling method is applied and a kind of
treatment for the object (such as an operation, a maintenance of a
low active condition or the like), a temperature at which the
object is to be kept (for example, a temperature to which the
object is to be cooled, or a temperature to which the object is to
be warmed), namely the predetermined temperature of the object is
determined upon the application of the selective temperature
controlling method using the extracorporeal circulation apparatus.
Therefore, the predetermined temperature at which the object is to
be maintained by means of the selective temperature controlling
method as well as an accuracy of such temperature maintenance is
properly selected by for example a doctor depending on the
treatment for the object.
Then, in the first aspect, the present invention provides an
extracorporeal circulation apparatus used for the selective
temperature controlling method (for example the selective cooling
method and/or the selective warming method) in which a temperature
of an object which is a part of a body is kept (or shifted (or
changed) and kept) at a predetermined temperature (T0), which
apparatus comprises: (A) a fluid replacement supply unit which
quantitatively supplies (or meters) a fluid replacement of which
temperature has been adjusted into a blood vessel (thus into an
interior of the body); (B) a blood concentration unit which
quantitatively withdraws (thus removes) blood diluted by the fluid
replacement from a blood vessel (thus from an interior of the body)
and concentrates the withdrawn diluted blood; and (C) a blood
supply unit which controls a temperature of the blood which has
been concentrated and quantitatively supplies (or meters) the
concentrated blood into a blood vessel (thus into an interior of
the body), the blood concentration unit comprising a diluted blood
temperature sensor which measures a temperature of the withdrawn
diluted blood, and the fluid replacement supply unit comprising a
means which controls (or adjusts) a temperature of the fluid
replacement to be supplied based on a different extent between the
measured diluted blood temperature (T1) and the predetermined
temperature of the object (T0) (such as a difference .DELTA.T
(=T1-T0), a ratio TR (=T1/T0) or the like). It is noted that the
means which controls the temperature of the fluid replacement to be
supplied serves to make the different extent smaller.
By means of the apparatus as described above, the control to keep
the object to which the selective temperature controlling method is
applied at a temperature which is close to the predetermined
temperature, and preferably substantially the predetermined
temperature can be carried out more accurately, so that the
selective temperature controlling method can be carried out more
effectively compared with using the prior art apparatus.
In the apparatus of the present invention, the diluted blood which
is withdrawn out is discharged from the object to which the
selective temperature controlling method is applied, and therefore
it is assumed that the temperature of the diluted blood measured by
the diluted blood temperature sensor (T1) represents the
temperature of the object to which the selective temperature
controlling method is applied. The term "represent(s)" herein is
intended to mean that the temperature of the diluted blood is not
necessarily the temperature of the object itself (although it is
preferably the temperature of the object itself), variation of the
diluted blood temperature or the diluted blood temperature being
relatively higher or lower corresponds to variation of the object
temperature or the object temperature being higher or lower.
Particularly, when the predetermined temperature at which the
object is to be maintained or the accuracy of the temperature
maintenance at the predetermined temperature is not so strict, the
above assumption is conveniently applicable.
Further, when a supply rate of the fluid replacement is large
depending on the treatment which is applied to the object so that a
withdrawal rate of the diluted blood is large, a temperature change
of the diluted blood during a period from the object to the diluted
blood temperature sensor, and in particular a temperature change
due to the body temperature may be neglected since the period
required for the diluted blood to flow from the object to the
outside of the body becomes short. In such case, it is often that
the temperature of the withdrawn diluted blood (T1) is regarded as
the temperature of the object at that time which is to be kept at
the predetermined temperature (T0).
In the apparatus of the present invention, the "means which
controls a temperature of the fluid replacement to be supplied
based on a different extent between the measured diluted blood
temperature (T1) and the predetermined temperature of the object
(T0)" is a means which obtains the different extent (such as a
difference or a ratio) between the measured diluted blood
temperature and the predetermined temperature of the object, and
increases or decreases the temperature of the fluid replacement to
be supplied based on the different extent. It is noted that when
there is substantially no different extent, the means keeps the
temperature of the fluid replacement as it is.
Concretely, when the diluted blood temperature (T1) is higher than
the predetermined temperature of the object (T0) (that is, when
T1-T0>0 or T1/T0>1, and thus for example when cooling by
means of the fluid replacement seems to be insufficient in the case
of the selective cooling or when warming by means of the fluid
replacement seems to be excessive in the case of the selective
warming), the above means functions to decrease the temperature of
the fluid replacement to be supplied. Such function can be achieved
by forming a control system which obtains the different extent
between the diluted blood temperature (T1) and based on the
different extent the predetermined temperature of the object (T0)
and warms and/or cools the fluid replacement to be supplied into
the inside of the body so as to make the different extent smaller.
The formation of such system is well known in the field of the
temperature control. For example, a manner can be employed in which
a set temperature of a heat exchanger (or a warming/cooing device)
which controls the temperature of the fluid replacement supplied
into the inside of the body is changed (that is, the set
temperature is lowered) depending on the measured temperature.
Also, when the diluted blood temperature (T1) is lower than the
predetermined temperature of the object (T0) (that is, when
T1-T0<0 or T1/T0<1, and thus for example when cooling by
means of the fluid replacement seems to be excessive in the case of
the selective cooling or when warming by means of the fluid
replacement seems to be insufficient in the case of the selective
warming), the above means functions to increase the temperature of
the fluid replacement to be supplied.
It is noted that when there is substantially no different extent
(that is, when T1-T0=0 or T1/T0=1, and thus for example when the
selective temperature controlling method seems to be working
satisfactorily), the above means functions to keep the temperature
of the fluid replacement to be supplied at that time.
In a case where the temperature of the blood diluted by the fluid
replacement may change after it has once reached a temperature
which is the same as that of the object in the object, the above
explanations are not applicable. Also, in a case where the blood
diluted by the fluid replacement is withdrawn without its
temperature having been thermally equilibrium with the object
because of a short residence time of the fluid replacement in the
object since a supply rate of the fluid replacement is too large
(especially at the beginning of the fluid replacement supply), the
above explanations are not applicable. If no change in T1 when the
supply rate of the fluid replacement is temporarily increased
and/or decreased a little, the above explanations will be
applicable. It is preferable to follow the supply rate which is
described concretely in the "Detailed Description of the Invention"
part of the present specification.
Alternatively, when the supply rate of the fluid replacement into
the inside of the body may be changed depending on the treatment
for the object, it is also possible to use a means which changes
the supply rate of the fluid replacement into the inside of the
body in place of or in addition to the above means which adjusts
the temperature of the fluid replacement. That is, it is utilized
that an amount of heat transferred from the fluid replacement to
the object or from the object to the fluid replacement changes when
the supply rate of the fluid replacement is changed. Generally,
when the supply rate is increased, an amount of heat transferred is
increased. That is, when the temperature of the fluid replacement
is lower than that of the object, the object is further cooled by
the increase of the supply rate of the fluid replacement. Also,
when the temperature of the fluid replacement is higher than that
of the object, the object is further warmed by the increase of the
supply rate of the fluid replacement, and when the supply rate of
the fluid replacement is decreased, reversed phenomena are
observed. This embodiment to change the supply rate is particularly
preferably used for changing the temperature of the object a
little.
In the second aspect, the extracorporeal circulation apparatus
according to the present invention comprises a supplied fluid
replacement temperature sensor in addition to the diluted blood
temperature sensor, and the former sensor measures a temperature of
the fluid replacement which is supplied to the inside of the body
(a supplied fluid replacement temperature, T2). In this apparatus,
an averaged value (Tav, an averaged temperature such as an
arithmetical mean, a logarithmic mean, a weighted mean or the like)
of the supplied fluid replacement temperature (T2) and the diluted
blood temperature (T1) is assumed to be represent the temperature
of the object to which the selective temperature controlling method
is applied in place of the diluted blood temperature (T1) in the
apparatus of the first aspect, and a different extent between the
averaged temperature (Tav) and the predetermined temperature of the
object (T0) is taken into consideration in place of the different
extent between the diluted blood temperature (T1) and the
predetermined temperature of the object (T0) in the apparatus of
the fist aspect. The temperature of the fluid replacement to be
supplied is controlled so that such former extent becomes smaller.
The other features are substantially the same as those of the
apparatus of the first aspect.
Thus, in the apparatus of the second aspect, the "means which
controls a temperature of the fluid replacement to be supplied
based on a different extent between the measured diluted blood
temperature (T1) and the predetermined temperature of the object
(T0)" in the apparatus of the first aspect is a means which obtains
the different extent between the predetermined temperature of the
object and the averaged temperature of the diluted blood
temperature and the supplied fluid replacement temperature, and
increases or decreases, or keeps the temperature of the fluid
replacement to be supplied based on thus obtained different extent.
That is, the different extent between the predetermined temperature
and the diluted blood temperature is considered while further
considering the supplied fluid replacement temperature. Similarly
to the apparatus of the first aspect as described above, the supply
rate change of the supplied fluid replacement may be applied in
place of or in addition to the control of the fluid replacement
temperature.
Concretely, when the averaged temperature (Tav) is higher than the
predetermined temperature of the object (T0) (that is, when
Tav-T0>0 or Tav/T0>1, and thus for example when cooling by
means of the fluid replacement seems to be insufficient in the case
of the selective cooling or when warming by means of the fluid
replacement seems to be excessive in the case of the selective
warming), the above means functions to decrease the temperature of
the fluid replacement to be supplied. When the averaged temperature
(Tav) is lower than the predetermined temperature of the object
(T0) (that is, when Tav-T0<0 or Tav/T0<1, and thus for
example when cooling by means of the fluid replacement seems to be
excessive in the case of the selective cooling or when warming by
means of the fluid replacement seems to be insufficient in the case
of the selective warming), the above means functions to increase
the temperature of the fluid replacement to be supplied. It is
noted that when there is substantially no different extent (that
is, when Tav-T0=0 or Tav/T0=1, and thus for example when the
selective temperature controlling method seems to be working
satisfactorily), the above means functions to keep the temperature
of the fluid replacement to be supplied at that time.
Also, in an embodiment where the temperature of the diluted blood
is changed after it has reached in the object the temperature of
the object, and in an embodiment where a supply rate of the fluid
replacement is too large, effects due to such embodiments are
lowered in the apparatus of the second aspect.
Similarly to the apparatus of the first aspect as described before,
the formation of a control system which obtains the averaged
temperature (Tav) of the supplied fluid replacement temperature
(T2) and the diluted blood temperature (T1), obtains the different
extent between the averaged temperature (Tav) and the predetermined
temperature of the object (T0), and controls the temperature and/or
the supply rate of the fluid replacement to be supplied is well
known to those skilled in the art.
In any aspect of the present invention, the diluted blood
temperature or the averaged temperature of the diluted blood
temperature and the supplied fluid replacement temperature is
regarded as described above to represent and preferably be equal to
the actual temperature of the object to which the selective
temperature controlling method such as the selective cooling method
is applied, and it is therefore preferable that the fluid
replacement and the diluted blood are not so thermally affected by
others as possible except the object. Thus, it is preferable that
the temperatures of the fluid replacement and the diluted blood are
measured as closely to the object as possible. Therefore, the
temperatures of the fluid replacement and the diluted blood are
measured at positions which are closest (namely, just vicinities)
to the body. It is preferable that for example, the diluted blood
is measured at a position which is immediately downstream of the
outlet of the diluted blood from the inside of the body, and the
supplied fluid replacement is measured at a position which is
immediately upstream of the inlet of the supplied fluid replacement
into the inside of the body.
In any aspect of the present invention, the withdrawn of the
diluted blood and the supply of the fluid replacement are carried
out through catheters as described below. In a particularly
preferable embodiment, a thermister is located at one end of each
of the catheters (one for the withdrawal of the diluted blood and
the other for the supply of the fluid replacement) which end is
closer to the body (i.e. the leading end when the catheter is
inserted) or a vicinity of such end. Such catheters are inserted
into the inside of the body so that the diluted blood temperature
and the supplied fluid replacement temperature are measured while
making the catheters located as near the object as possible to
which the selective temperature controlling method is applied and
the diluted blood temperature and the supplied fluid replacement
temperature are measured, whereby the accuracy of the object
temperature assumption is improved so that the accuracy of keeping
the object at the predetermined temperature is improved.
In any aspect of the present invention, the apparatus according to
the present invention comprises in a particularly preferable
embodiment comprises a fluid replacement supply unit which cools or
warms the fluid replacement to a temperature lower or higher than
the body temperature and quantitatively supplies the fluid
replacement into a blood vessel, a blood concentration unit which
quantitatively withdraws the diluted blood from a blood vessel and
concentrates the diluted blood preferably so as to reach a
hematocrit value of at least 70% of that before being diluted
(usually, a normal hematocrit value of a patient to whom the
selective temperature controlling method is applied), and a blood
supply unit which controls a temperature of the concentrated blood
to a temperature near the body temperature and supplies the
concentrated blood into a blood vessel.
When the selective temperature controlling method is applied using
the apparatus according to the present invention, it is generally
preferable to supply the fluid replacement which has been adjusted
to the predetermined temperature (T0) beforehand upon starting to
use the apparatus. Particularly, when the apparatus of the second
aspect is used, since the supplied fluid replacement temperature
(T2) is measured, it is preferable to control the temperature of
the supplied fluid replacement such that T2 becomes the
predetermined temperature (T0). Upon such control, it is desirable
to take effects of various parameters (or factors, including a room
temperature) into the consideration as described below.
In a case where the selective temperature controlling method is
applied using the apparatus according to the present invention, it
may be not preferable to rapidly change (for example cool or warm)
the temperature of the object to the predetermined temperature (T0)
when the predetermined temperature is greatly different from the
temperature of the object before the application of the selective
temperature controlling method (usually the body temperature in a
normal condition). This is because the rapid temperature change of
the object gives a certain shock, and for example electrolyte
balance is broken, which may not be preferable. Thus, in such case,
a manner is preferably employed in which a provisional
predetermined temperature (T0-1) which is near the temperature
before the application and which is between the temperature before
the application and the predetermined temperature is set so that
the temperature of the object reaches T0-1 first, then a next
provisional predetermined temperature (T0-2) is set by shifting the
provisional temperature toward the predetermined temperature a
little so that the temperature of the object reaches T0-2, and then
an additional next provisional predetermined temperature is set if
necessary, . . . , and the temperature of the object finally
approaches the original predetermined temperature (T0) in
steps.
For example, in a case in which the object is to be cooled from
37.degree. C. to 25.degree. C. as the predetermined temperature
(T0), the provisional predetermined temperature (T0-1) is first set
at 35.degree. C. so that the object temperature reaches 35.degree.
C., then the next provisional predetermined temperature (T0-2) is
set at 33.degree. C. when the object temperature approaches or
reaches 35.degree. C. so that the object temperature reaches
33.degree. C., . . . , whereby the object temperature thus
approaches 25.degree. C. as the original predetermined temperature
(T0) in steps. The manner in which the object temperature
approaches the predetermined temperature may be stepwise as
described above or continuous. When the object temperature is
raised reversely, the above is applicable similarly. When the
object is warmed, similar is applicable. It is of course possible
to rapidly cool or warm if no problem occurs when the object
temperature is changed to the predetermined temperature
rapidly.
When the object temperature is adjusted to the predetermined
temperature (T0) by applying the apparatus of the present invention
to the selected object, in one embodiment a temperature of the
fluid replacement to be supplied is controlled first by means of a
fluid replacement temperature controller such that the temperature
of the fluid replacement to be supplied becomes T0 (which may be
the provisional temperature as the above). The fluid replacement
thus controlled is supplied into the inside of the body.
When the apparatus of the first aspect is used for the supply of
such fluid replacement, the diluted blood temperature (T1) is
measured, and then the fluid replacement temperature controller
which has been set at the predetermined temperature (T0) is re-set
based on the measurement of the diluted blood temperature, that is
the temperature of the fluid replacement to be supplied in the
fluid replacement temperature controller is re-adjusted (namely,
the temperature is set higher or lower than T0 or the temperature
is kept). Also, when the apparatus of the second aspect is used,
the supplied fluid replacement temperature (T2) is further measured
followed by obtaining the average temperature of the supplied fluid
replacement temperature (T2) and the diluted blood temperature
(T1), and then the averaged temperature is compared with the
predetermined temperature (T0) followed by controlling the fluid
replacement temperature controller again. It is noted that with
regard to the predetermined temperature (T0), it may be preferable
to set a provisional predetermined temperature, based on which the
fluid replacement temperature controller is adjusted followed by
gradually shift the provisional predetermined temperature so that
the original predetermined temperature is finally reached as
described above.
After having made the object temperature reach the predetermined
temperature, returning the object temperature to the original
object temperature (that is, recovering the object temperature)
truly corresponds to warming the object to the predetermined
temperature. Therefore, the apparatus according to the present
invention may be used for a temperature recovering method in which
a temperature of the object is returned to its original temperature
of the object which has been shifted to the predetermined
temperature by the selective temperature controlling method. That
is, the selective warming method after carrying out the selective
cooling method or vice verse may be carried out by using the same
apparatus.
It is noted in a case in which the object temperature is shifted to
the predetermined temperature, and in particular the object is
warmed, that it may be preferable to use oxygen containing blood
when the object needs oxygen for the purpose of its metabolism.
That is, it may be preferable that not using for example a Ringer's
solution as the fluid replacement, at least a portion and
optionally most of the fluid replacement is replaced with blood
(autologous blood or transfusion blood) as described below. When
the blood is supplied as above, it is preferable that the blood is
oxygen oxygenated by for example an artificial lung. In this
embodiment, warming is applicable to a case in which the object is
warmed from its normal temperature to a higher temperature as well
as a case in which the object is returned from its selectively
cooled temperature to its original normal body temperature.
It is noted that the present invention also provides an
extracorporeal circulation method for the selective temperature
controlling method. The former method is an extracorporeal
circulation method for keeping an object at a predetermined
temperature for the selective temperature controlling method, which
comprises the steps of: (A) quantitatively supplying (or metering)
fluid replacement of which temperature has been adjusted into a
blood vessel by means of a fluid replacement supply unit; (B)
quantitatively withdrawing blood diluted by the fluid replacement
from a blood vessel and concentrating the withdrawn blood by means
of a blood concentration unit; and (C) controlling a temperature of
the blood which has been concentrated and quantitatively supplying
the blood into a blood vessel by a blood supply unit, and the
method being characterized in that a temperature of the withdrawn
diluted blood is measured by means of the blood concentration unit,
and a temperature of the fluid replacement which is quantitatively
supplied by the fluid replacement supply unit is controlled based
on a different extent between the measured diluted blood
temperature and the predetermined temperature of the object.
The fluid replacement supply unit measures the temperature of the
fluid replacement to be quantitatively supplied and may control the
temperature of the fluid replacement based on a different extent
between the predetermined temperature and an averaged temperature
of the supplied fluid replacement temperature and the diluted blood
temperature in place of the different extent between the measured
diluted blood temperature and the predetermined temperature of the
object.
Also, temperature control of the fluid replacement to be
quantitatively supplied is preferably carried out while considering
heat transfer between the fluid replacement and a surrounding of
the apparatus until the fluid replacement is supplied into the
blood vessel. In addition, it is preferable that the temperature of
the fluid replacement to be quantitatively supplied has been
adjusted to the predetermined temperature of the object when
starting the above method. In other words, the present invention
provides an extracorporeal circulation method in which the
extracorporeal apparatus according to the present invention as
described above or described in detail below is used.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a schematic drawing which shows the apparatus according
to the present invention;
FIG. 2 is a schematic drawing of the apparatus shown in FIG. 1
which further comprises an artificial lung for oxygenating a
portion of diluted blood (only a part of the lung being shown);
FIG. 3 is a schematic drawing of the apparatus shown in FIG. 1
which further comprises an artificial lung for oxygenating
autologous blood or transfusion blood (only a part of the lung
being shown);
FIG. 4 is a schematic drawing of the apparatus shown in FIG. 1
which further comprises an artificial lung for oxygenating fluid
replacement (only a part of the lung being shown); and
FIG. 5 is a schematic drawing of the apparatus shown in FIG. 1
which comprises in place of an artificial lung, a drip chamber for
bubbling oxygen gas.
LIST OF NUMERALS 1 . . . liquid supply pump, 3 heat exchanger, 4 .
. . supplied fluid replacement temperature sensor, 5 . . .
withdrawal pump, 6 . . . heat exchanger, 7 . . . water removal
pump, 8 . . . fluid replacement container, 9 . . . drip chamber,
10, 11 . . . catheter, 12 . . . drip chamber, 13 . . . blood
concentration element, 14 . . . removed water tank, 15 . . .
catheter, 17 . . . body, 18 . . . heparin supplier, 19 . . .
supply/removal controlling mechanism, 20 . . . diluted blood
temperature sensor, 24 . . . object, 100 bypass line, 102 . . .
dialysate.
DETAILED DESCRIPTION OF THE INVENTION
The term "selective temperature controlling (or adjusting) methods"
is a method which shifts a temperature of an object as a part of a
body to a predetermined temperature so as to keep the object in a
condition in which a predetermined purpose can be achieved, and
which includes the "selective cooling method" and "selective
warming method." Also, the "selective temperature controlling
method" includes a method in which the temperature of the object is
returned to its original temperature thereafter. The term
"selective cooling method" is a method which is used in a medical
treatment field, and particularly in a brain surgery field, and it
concretely means a method wherein a part of a body as the object
(for example, an organ such as a brain) is selected and that part
is locally cooled. The selective cooling method is a locally
cooling method used for example in a case in which bleeding is
expected (for example a case of an operation of a limited part of a
body (for example, a head)) or a case in which a metabolism or an
activity of an organism function is suppressed locally and
temporarily during which various procedures or treatments are
carried out. While the "selective cooling method" is to cool the
object, the "selective warming method" is merely different in that
the object is warmed, and it is applicable for the treatment of for
example a cancer, a frostbite or the like. As described above,
temperature recovery after cooling may be included by the selective
warming method. Further, the temperature recovery after warming may
also be included by the selective cooling method.
The present invention is based on the following concept: The fluid
replacement of which temperature has been adjusted is injected
through a blood vessel into an artery at a certain position thereof
which directly or indirectly leads to the object of which
temperature is to be controlled, the blood diluted by the fluid
replacement is withdrawn through a blood vessel from a vein at a
certain position thereof which directly or indirectly leads to the
object, then the diluted blood is concentrated so as to recover the
blood which is similar to before being diluted and preferably which
is substantially equivalent to the blood before being diluted, and
the recovered blood is returned through a blood vessel to a vein at
a position thereof closer to a heart (so-called a heart side
position) which directly or indirectly leads to said vein from
which the diluted blood is withdrawn after a temperature of the
recovered blood is adjusted (for example returned to a temperature
of the human body), so that a temperature of the object is safely
and selectively adjusted to the predetermined temperature without
changing and preferably without substantially increasing an amount
of body fluid kept in the body.
For example, when the selective cooling method is applied to a
brain, the fluid replacement is supplied at a neck portion into an
arteria vertebralis, the diluted blood is withdrawn from a jugular
vein, and the concentrated blood is returned into the inside of the
body through for example a femoral artery. Also, for example for
the application to liver, the fluid replacement is supplied through
a hepatic artery, the diluted blood is withdrawn from an
appropriate vein, and the concentrated blood is returned into the
body at a position of a vein closer to the heart which directly or
indirectly connects to said appropriate vein. Generally, the fluid
replacement is supplied to an artery which belongs to the object to
which the selective cooling method is applied. The vein from which
the diluted blood is withdrawn is preferably closely related to an
artery which belongs to the object (and thus the vein collects a
large amount and preferably the largest amount of the blood which
has passed through said artery). Although the position at which the
concentrated blood is returned is not particularly limited,
generally the position is at the vein. When this vain is the same
as the vein from which the diluted blood is withdrawn, the
concentrated blood is returned to a position closer to the heart.
In order that a temperature change of the diluted blood as small as
possible after it has reached the object temperature, the diluted
blood is preferably withdrawn from a position which is as close to
the object as possible.
By carrying out the selective cooling method using the apparatus
according to the present invention, problems such as a troublesome
operation of a heart-lung machine under a cardiac arrest, and
various risks such as bleeding are solved while avoiding for
example extreme overhydration, so that a cerebral hypotension
condition (for example, a local low irrigation condition) is stably
ensured.
In the apparatus according to the present invention, the
concentrated blood temperature is adjusted before it is returned to
the body inside, and such adjustment is preferably carried out by
heat exchange, and particularly by indirect heat exchange. An
apparatus having a heater and/or a cooler for that purpose is not
particularly limited. In any case, it is possible that the
predetermined temperature of the concentrated blood is achieved by
immersing a conduit through which the concentrated blood flows in a
constant-temperature bath set at a predetermined temperature, and
such heat exchanging manner is preferable. In one embodiment, when
it has been known beforehand that only warming or cooling is
carried out, the heat exchanger may comprise only a heater or a
cooler.
The fluid replacement (or a diluent) used in the present apparatus
is not particularly limited as far as it is able to be cooled or
warmed in an appropriate manner, and it is able to be used for
cooling or warming the object in the body while it is supplied into
the body through a blood vessel so as to dilute the blood.
Generally, the fluid replacement at least does not effect adversely
the intended treatment, and preferably the fluid replacement helps
such treatment. Concretely, an aqueous solution which contains a
nutrient and/or an electrolyte may be exemplified as the fluid
replacement, and an isotonic solution such as a Ringer's solution,
a lactated Ringer's solution, a Ringer's solution containing a low
molecular dextrin (for example containing 5%) or the like is
preferably used as the fluid replacement, but not limited
thereto.
In one embodiment, the apparatus according to the present invention
comprises a fluid replacement temperature controller as the means
to adjust a temperature of the fluid replacement to be supplied.
The controller may be the indirect heat exchanger as described
above, and for example one in which an appropriate liquid (which is
usually water) as a heat transfer medium is charged in a vessel
equipped with a heater or a cooler and a tube which supplies the
fluid replacement is located in the liquid in for example a spiral
form may be used. By controlling a temperature of the liquid using
the heater and/or cooler, the temperature of the fluid replacement
at the exit of the fluid replacement temperature controller (T3)
can be controlled.
It is noted that when a liquid such as the fluid replacement, blood
or the like is warmed and/or cooled, the apparatus comprising a
heating means (for example, an electric resistive heater) and/or a
cooling means (for example, a cooler using a coolant) may be used
as described above, and in a preferable embodiment, an
warming/cooling apparatus comprising a Peltier element is used. It
is noted that warming includes a case in which a temperature is
returned to an original temperature after cooling, and that cooling
includes a case in which a temperature is returned to an original
temperature after warming, both of which may be referred to as
temperature returning.
The warming/cooling apparatus comprising the Peltier element warms
or cools depending on an electric current direction (thus,
polarity) across the element, and a thermal dose upon warming or
cooling depends on an amperage. When the Peltier element is used,
switching between warming and cooling may be carried out freely
electrically and the amperage may be increased and decreased easily
and precisely so that response and sensitivity of the temperature
control are good and the temperature control is accurate. The
Peltier element has been known for a long time, it has not known or
done that its advantage is very conveniently utilized when the
features of the element are combined in the extracorporeal
circulation apparatus which may be used for various treatments in
the medical field.
For example, the temperature of the fluid replacement, the blood or
the like immediately after leaving the warming and/cooling
apparatus is measured, and the measured result is fed back to a
controller of the warming and/cooling apparatus, so that increase
or decrease of an amount of the electric current through the
Peltier element and switching of its polarity may be carried out
with a good sensitivity and accuracy. The body condition of a
patient who uses the extracorporeal circulation apparatus may
change momentarily, and when the apparatus according to the present
invention is used, such change can be detected through T1. Thus, it
is preferable that an extent of warming/cooling of the fluid
replacement to be supplied into the body, the blood to be returned
to the body or the like is freely changed and switching between
warming and cooling is freely carried out, and in order to be thus
preferable, the warming/cooling apparatus comprising the Pertier
element is preferably used, which is particularly preferable for
controlling the temperature recovery.
More particularly, when an electric current is passed across the
Peltier element, one junction thereof fevers to be at a higher
temperature and the other junction thereof absorbs heat to be a
lower temperature, and when the polarity of the voltage applied to
the Peltier element is reversed, the temperature relationship
between the junctions is reversed. Usually, one junction is warmed
or cooled by using air at a room temperature, and for example by
blowing air using a fan so that a thermal energy is transferred
between the junctions. Usually, thus warmed or cooled junction is
contacted with the fluid replacement, the blood or the like
indirectly (for example through a plastic film, a metal thin film
or the like) for the heat exchange. Using the warming/cooling
apparatus comprising the Peltier element as described above results
in compactness of the extracorporeal circulation apparatus, space
saving, improved operability and so on may be achieved.
The fluid replacement which leaves the fluid replacement
temperature controller flows through a certain length of a conduit
until supplied into the body, during which a temperature of the
fluid replacement is affected by a temperature of its surrounding
circumstance (i.e. a room temperature) so that the supplied fluid
replacement temperature (T2) is often different from the
temperature of the fluid replacement upon leaving the fluid
replacement temperature controller (T3). For example, when the
surrounding temperature is higher than the temperature of the fluid
replacement upon leaving the fluid replacement temperature
controller (T3), T2 is higher than T3, and when the surrounding
temperature is lower, T2 is lower than T3. Therefore, there is
usually a substantive temperature difference .DELTA.T (=T3-T2) is
present. In the present apparatus, it is preferable to take this
temperature difference .DELTA.T into account when the fluid
replacement temperature is adjusted based on the different extent
between the average temperature of the diluted blood temperature
(T1) and the supplied fluid replacement temperature (T2) and the
predetermined temperature (T0). That is, in a preferable embodiment
according to the present invention, the temperature of the fluid
replacement temperature controller (T3) is controlled considering
the temperature change of the fluid replacement between leaving the
fluid replacement temperature controller and going into the body,
namely the heat absorption from or the heat radiation into the
surrounding circumstance of the apparatus.
Usually, the temperature difference is affected by parameters such
as operation conditions of the apparatus (for example, a kind of
the fluid replacement and its supply rate, a material of the
conduit for supplying the fluid replacement and a diameter of the
conduit), the temperature of the circumstance surrounding the
apparatus (i.e. a room temperature, T4) and so on. Therefore, when
relationships between the temperature difference .DELTA.T and the
parameters have been obtained beforehand as calibration curves by
varying the parameters variously, it can be seen which temperature
should be set in the fluid replacement temperature controller (T3)
so as to achieve an aimed T2 under specific parameter conditions.
Since T2=T0 is generally preferable at the beginning of the
operation, T3 may be obtained based on the temperature difference
between the T2(=T0) and T1 in the initial stage of the
operation.
Particularly, in the apparatus according to the second aspect in
which the diluted blood temperature (T1) and the supplied fluid
replacement temperature (T2) are measured, the average of these
temperature is assumed to be the object temperature, the different
extent between the average and T0 is considered and T2 is selected
such that the different extent becomes smaller. Upon such
selection, the temperature difference (.DELTA.T) is considered and
the set temperature of the fluid replacement temperature controller
(T3) is selected (=T2+.DELTA.T), so that the temperature (T2) can
be precisely controlled.
That is, since the diluted blood temperature (T1) is measured and
the predetermined temperature of the object T0 is determined
beforehand, T2 which lowers the different extent is obtained by for
example T2=2T0-T1. Further, .DELTA.T can be obtained with reference
to the calibration curves which were obtained under the specific
parameter conditions, and the set temperature of the fluid
replacement temperature controller (T3) may be obtained by
T3=T2+.DELTA.T considering the obtained T2 and .DELTA.T, and the
fluid replacement temperature controller is set at thus obtained
T3.
In order to obtain a temperature of a liquid which is flowing
through a length of a conduit while considering the heat transfer
to its surrounding circumstance, various model equations are
conceivable, and any model equation may be used as for as it does
not substantially affect the applied selective temperature
controlling method adversely. Concretely, the following model
equation for example may be used in place of the calibration curves
as described above, so that the heat transfer between the liquid
and its surrounding circumstance is considered so as to obtain the
set temperature of the fluid replacement temperature controller
(T3):
(wherein l is a length (m) of the conduit between the fluid
replacement temperature controller and a position at which a
supplied fluid replacement temperature is measured, Tt is a
temperature (.degree.C.) of the fluid replacement at a time of t
(second) supplied into the body, v is a supply rate (linear
velocity, m/s) of the fluid replacement, and a=.alpha.A/V (wherein
.alpha. is a heat transfer coefficient (W/m.sup.2 K) of a material
of the conduit, A is a total surface area (m.sup.2) of the conduit,
and V is a volume (m.sup.3) of the fluid replacement in the
conduit)). It is noted that Equation (I) has been obtained from a
general equation of the heat transfer.
In one case, the fluid replacement temperature Tt may be regarded
to change linearly during the fluid replacement flows between the
fluid replacement temperature controller and the position at which
the supplied fluid replacement temperature is measured. In such
case, the fluid replacement temperature Tt can be expressed by the
following equation:
By substituting this equation in the above integral expression
equation followed by numerical calculation, the temperature of the
fluid replacement controller (T3) may be obtained as to the aimed
T2. Other equation which can express Tt may be similarly used so as
to obtain the temperature of the fluid replacement controller
(T3).
Alternatively, in place of the above Equation (I), the following
equation (II) may be used:
in which b=4.alpha.al/(pdCp) (wherein a is a heat transfer
coefficient (W/m.sup.2 K) of a material of the conduit, l is a
length (m) of a conduit between the fluid replacement temperature
controller and the position at which the supplied fluid replacement
temperature is measured, .rho. is a specific gravity (kg/m.sup.3)
of the fluid replacement, d is an outer diameter (m) of the
conduit, Cp is a specific heat capacity (J/kg.multidot.K) of the
fluid replacement, and v is a supply rate (linear velocity, m/s) of
the fluid replacement) This equation may be obtained by forming a
differential equation which expresses that an amount of heat loss
of the fluid replacement into its surrounding during the fluid
replacement flows over a very small length is equivalent to an
amount of heat gain by the surrounding, solving the differential
equation and integrating using boundary conditions that the fluid
replacement temperature is T3 and T2 when the length of the conduit
is zero and 1, respectively. It is noted that those skilled in the
art can derive this equation easily with reference to for example
"Zukai: Dennetu-kogaku no Manabikata (Illustration: How to learn
heat transfer engineering)" (1st edition, by N.Kitayama, published
by Ohmsha (Tokyo), Jul. 20, 1989, pp 104-109).
The apparatus according to the first aspect does not measure the
supplied fluid replacement temperature (T2), but the heat transfer
between the fluid replacement and the surrounding until the fluid
replacement of which temperature has been adjusted is supplied into
the blood vessel is considered upon controlling the temperature of
the fluid replacement to be supplied. That is, when the fluid
replacement temperature which has been adjusted is expected to
become increased until the entry of the body, the fluid replacement
is adjusted to be lower beforehand by such temperature increase
(which is thus similar to .DELTA.T). In the opposite case, the
fluid replacement is adjusted to be higher beforehand by
.DELTA.T.
In one preferable embodiment, the apparatus according to the
present invention comprises an artificial lung which can oxygenate
the fluid replacement, the blood and/or the diluted blood to be
supplied to the body. The artificial lung may be any device which
has a function to increase an amount of dissolved oxygen in the
fluid replacement, the blood or the diluted blood, so-called an
oxygen addition function or an oxygenation function, and for
example a membrane type and a bubbling type may be used. In a
particularly preferable embodiment, a portion of the diluted blood
is divided into a side stream without being concentrated and
supplied to the artificial lung where it is oxygenated, and the
oxygenated diluted blood is supplied into the body again together
with the fluid replacement after subjected to the temperature
adjustment by the fluid replacement temperature controller. In an
alternative preferable embodiment, the fluid replacement is
introduced to the artificial lung where it is oxygenated, and then
supplied into the body.
In one of other preferable embodiments (for example in a case where
the object to which the selective temperature controlling method is
applied metabolizes), the apparatus according to the present
invention supplies to the body, in place of the fluid replacement
as described above, autologous blood drawn from a patient to be
treated and/or transfusion blood together with the fluid
replacement. Upon such supply, the autologous blood and/or the
transfusion blood is preferably introduced to the artificial lung
where it is oxygenated. In other embodiment, it is possible to
oxygenate by providing, in place of such artificial lung, a chamber
which holds a liquid such as the diluted blood, the fluid
replacement or the blood and by bubbling the liquid with oxygen (or
air) while blowing it into the liquid.
In the apparatus of the present invention, the concentration of the
diluted blood means that a hematocrit value of the diluted blood
drawn from the body (thus which value is smaller than a hematocrit
value of original (i.e. before being diluted) blood) is increased
or recovered, and concretely it is carried out by filtration or
dialysis (hereinafter which are generically referred to as a
filtration treatment). The filtration treatment may be carried out
by a hemofilter, a dialyzer or the like which is generally used as
an artificial kidney. In the apparatus according to the present
invention, the blood after being concentrated has a hematocrit
value of usually at least about 70% of, preferably at least about
90% of, more preferably at least about 95% of and most preferably
substantially the same as that of the blood before being
diluted.
When the dialyzer (or dialysis device) is used for the
concentration of the diluted blood in the apparatus of the present
invention, there is an advantage that balance of electrolytes
and/or nutrients of the patient to whom the selective temperature
controlling method is applied can be kept, or the balance which has
been destroyed can be recovered since dialysate contains the
electrolytes and/or the nutrients which are transferred to the
diluted blood and excessive electrolytes and/or waste products
which are not required by the body are removed by the dialysate.
Thus, the blood concentration unit may be preferably a hemodialysis
device (including a continuous hemodialysis (CHD) device), or a
hemodiafiltration device (including a continuous hemodiafiltration
(CHDF) device).
In fact, in a certain embodiment in which the apparatus according
to the present invention is used, a hematocrit value of a normal
person (about 40 to 50%) is generally diluted to a hematocrit value
of about 5 to 20%, for example about 7%, and such hematocrit value
of the diluted blood is recovered up to about 30 to 50% after being
concentrated. Therefore, a hematocrit value recovery ratio (a
hematocrit value after concentrated/a hematocrit value before
concentrated) is about 0.7 to 1.00.
One embodiment of the apparatus of the present invention is an
extracorporeal circulation apparatus for carrying out the selective
cooling method which is used for selectively cooling a region of
the object to the predetermined temperature. Also, in other
embodiment, there is provided an extracorporeal circulation
apparatus which is used for carrying out the selective, not
cooling, but warming method to the predetermined temperature. Such
apparatus may be used for warming the object to a high temperature
at which a cancer cell may be killed but a normal cell is not
affected. Concretely, it has been found that the cancer cell is
killed at about 42.degree. C., and the apparatus may be used for
warming only an object in which such cell are present.
The present invention will be explained hereinafter in detail with
reference to the accompanying drawings.
FIG. 1 is a diagram (flow sheet) which schematically shows the
extracorporeal circulation apparatus of the present invention,
which comprises (A) the fluid replacement supply unit, (B) the
blood concentration unit and (C) the blood supply unit (these units
are delimited by the alternate long and short dash lines).
The fluid replacement supply unit (A) comprises a fluid replacement
container (8), a fluid replacement pump (1) (with functions of
metering a pumping rate and its adjustment) which supplies the
fluid replacement into the body (17), a fluid replacement
temperature controller (3) and a drip chamber for fluid replacement
(9), and the temperature of the fluid replacement which is supplied
into the body (T2) is measured by a supplied fluid replacement
temperature sensor (4).
Also, the shown extracorporeal circulation apparatus comprises the
blood concentration unit (B), which comprises a blood pump (5)
which draws the diluted blood from the body (17) (i.e. carries out
the blood removal), and finally returns recovered concentrated
blood into the body (17), an anticoagulant (such as heparin, fusan
or the like) supplier (18), a drip chamber for blood (12), a blood
concentration device such as a filter for filtration (or a
dialyzer) (13), and a removed water tank (14), and optionally a
water removal pump (7), and the temperature of the drawn diluted
blood (T1) is measured by a diluted blood temperature sensor (20).
It is noted that a fluid replacement tank (22) is provided in the
blood concentration unit so as to fill conduits and elements in the
apparatus with the fluid replacement upon starting the apparatus
operation.
Further, the shown extracorporeal circulation apparatus comprises
the blood supply unit (C) which comprises a drip chamber for blood
to be returned (16) and a heat exchanger (6) for adjusting the
temperature of the concentrated blood. In order to control the
temperature of the concentrated blood, the heat exchanger has a
temperature sensor (50).
Appropriate conduits (such as a silicone tube, a polyvinyl chloride
tube or the like, shown with thicker lines in the drawing) connect
between those units or elements which constitute the units, and
required connections between the body (17) and each units are
formed by means of catheters (10, 11 and 15).
In the fluid replacement supply unit (A), the fluid replacement
pump (1) quantitatively injects into the body (17) the fluid
replacement usually at 10 to 800 ml/min., preferably 50 to 500
ml/min. and more preferably 100 to 400 ml/min. A practical supply
rate of the pump is appropriately selected within those ranges
depending on a purpose of the treatment for the object. As the pump
which can quantitatively deliver (thus meter) the fluid
replacement, a roller pump may be exemplified which is often used
for the delivery of blood. It is noted that in order to carry out
the speedy temperature adjustment of the object, the supply rate
are preferably relatively large, and for example a supply rate in
the range 100 to 400 ml/min. is further preferably used
(particularly in the case of a brain of an adult as the object in
the selective cooling method). In place of the roller pump, a
centrifugal pump may be used, wherein an appropriate flow rate
control means such as a valve, an inverter function or the like is
preferably combined.
When the supply rate of the fluid replacement is controlled by for
example a motor rotational speed of the fluid replacement pump (1),
a flow meter is not necessarily provided as an additional element,
but it may be located in a fluid replacement line so as to confirm
the supply rate of the fluid replacement. The flow meter may be for
example a electromagnetic flow meter. Further, the pump preferably
has a control function which makes the supply rate as predetermined
when it is not so (for example, a function to change the rotational
speed of the pump motor (such as an inverter function) or a
function to change a pressure loss of a conduit (such as a valve)).
When the quantitative supply of the fluid replacement pump (1) is
ensured, the flow meter may be omitted, and in this sense, the
shown apparatus has no flow meter. Generally, a flow meter may be
provided in any conduit through which a fluid has to be supplied at
a predetermined flow rate, and combination of the flow meter with a
pump ensures a predetermined flow rate (thus quantitative draw or
supply). As to the other pumps (5 and 7), the same as to the pump
(1) is applicable except the flow rate ranges as described
above.
The container (8) may be a plastic vessel or bag in which the fluid
replacement is enclosed, or may be a tank in which the fluid
replacement taken out from such container is stored. There are
provided the drip chamber (56) and a fluid empty detector (44)
between the container (8) and the pump (1). The fluid replacement
supply unit may further include in addition to the above described
elements, other drip chamber (9, having a pressure gauge P) for the
removal of bubbles, which removes the bubbles entrained with the
fluid replacement. Similar drip chambers (12 and 16) are provided
in the blood concentration unit and the blood supply unit,
respectively. It is noted that a filter (40) may be provided so as
to remove contaminants in the fluid replacement and a bubble
detector (42) may be provided for check the presence of the bubbles
in the fluid replacement.
The apparatus according to the present invention comprises the
blood concentration unit which quantitatively withdraws the diluted
blood from a blood vessel and usually a vein through which the
diluted blood flows after passing the object, and concentrates the
diluted blood preferably to an original hematocrit value of the
blood. Such unit requires a withdrawal supply pump (5) which
quantitatively withdraws the diluted blood from the body (17) and
supplies and finally returns the blood into the body and an element
(13) which concentrates the diluted blood which is withdrawn and
supplied thereto. It is noted that in addition to the fluid
replacement, blood is supplied to the object through the blood
vessel to which the fluid replacement is supplied and the other
blood vessels, so that the blood which leaves the object is in a
condition diluted by the fluid replacement. Optionally, a balloon
catheter may be inserted into only an artery which leads to the
object so as to substantially stop the blood flow and only the
fluid replacement is supplied to the object, and the fluid
replacement may be supplied through the catheter. Also, as to the
withdrawal of the diluted blood, a balloon catheter may be inserted
into only a vein which leads from the object so as to withdraw
substantially all the diluted blood to outside of the body.
The pump (5) preferably quantitatively withdraws the diluted blood
through the catheter (11) at a rate in the range usually 10 to 600
ml/min., preferably 50 to 400 ml/min., and more preferably 80 to
300 ml/min. from the body (particularly in the case of a brain of
an adult as the object in the selective cooling method). The
practical flow rate of the pump (5) may be selected as required
within such ranges depending on a purpose of the treatment. As the
pump (5), one which is of the same type of that of the fluid
replacement pump (1) may be used, and it may be cooperated with a
flow meter (not shown) as described above.
Upon using the apparatus of the present invention, the diluted
blood is drawn by means of the catheter (11) through a vein from
the region to be selectively cooled, and it is introduced through
the liquid transport pump (5) to a blood side inlet of the blood
concentration element (13) which is preferably a disposable
product.
In the apparatus of the present invention, the concentration
element (13) is preferably a dialysis device (in which a dialysate
(102) is supplied to the concentration element (13) as shown) or a
filtration device as described above, and the control of the
element is preferably carried out based on the hematocrit values as
measures before the blood is diluted and after the blood is
concentrated. Measurement of the hematocrit value may be conducted
by obtaining a volume percentage (%) of red blood cells after the
concentrated blood is subjected a centrifugation treatment.
It is convenient to measure a flow rate of the supplied fluid
replacement and a flow rate of liquid discharged out from the
concentration element (13) (which is also referred to as
"filtrate") as well as a total amount of the fluid replacement
which has been supplied and a total amount of the filtrate which
has been discharged, and to control a patient not to be in an
excessive overhydration condition or not to be in an excessive
dehydration condition, and usually such control is sufficient. It
is noted that when the dialysis device is used as the concentration
element (13), an amount of the dialysate which has been supplied to
the dialysis device is included in an amount of the filtrate, and
thus such amount of the dialysate has to be deducted from the
amount of the filtrate.
The concentration element (13) may include a pump (7) on its
filtrate side when necessary, so that a pressure difference across
the concentration element (13) can be further increased (and thus a
controllable range of the filtration pressure (or a pressure
difference upon the dialysis operation) is enlarged), whereby a
filtrate rate becomes more versatile due to using the pump (7). The
concentration element (13) of course dehydrates by means of only
the pressure difference produced by the pump (5) between the
diluted blood side (a delivery pressure) and the permeate side
(atmospheric pressure) produced by the pump (5), which is so-called
natural filtration or natural dehydration (or water removal). In
the case of the natural dehydration, the filtrate is collected in
the filtrate container (14) without passing through the pump
(7).
When the pump (1) is running, the filtrate rate from the
concentration element (13) (Vb ml/min., provided that supply rate
of the dialysate is deducted from Vb in the case of the dialysis
operation) is preferably substantially smaller than a supply rate
of the fluid replacement supplied into the body (Vd ml/min.) so
that a hematocrit value of the blood in the body is kept not higher
than before the beginning of the treatment. This is based on an
idea that in order to make the temperature adjusting effect by
means of the fluid replacement effective, it is preferable to
temporarily keep a certain amount of the fluid replacement within
the region of the object. Therefore, in a preferable embodiment of
the apparatus according to the present invention, the flow rates
are controlled to satisfy the relationship of
0.1Vd.ltoreq.Vb.ltoreq.Vd (wherein Vd.noteq.0). When Vb is smaller
than 0.1Vd (i.e. Vb<0.1Vd), an amount of the body fluid is
considerably excessive temporarily, which is not preferable. On the
other hand, when Vb is substantially larger than Vd, excessive
concentration of the blood occurs, which is not preferable.
However, Vb being larger than Vd is not completely excluded in the
apparatus of the present invention, and Vb may be larger than Vd if
no adverse effect occurs in the treatment where the apparatus of
the present invention is used.
In the apparatus of the present invention, the fluid replacement is
made of an aqueous solution of a low molecular material (such as an
electrolyte, a saccharide (for example glucose)) as a main
component. A total amount of the filtrate (provided that an amount
of the dialysate is deducted in the case of the dialysis device as
the concentration element) during the operation of the apparatus of
the present invention is most preferably substantially the same as
a total amount of the fluid replacement which has been supplied
during the operation, which means that operation times of the pump
(1) and the pump (5) and optionally the pump (7) may be different,
and that even though the pump (1) is being stopped, the pump (5)
may be being operated so that Vb is a some substantive rate under
the consideration of the preferable relationship of
0.1Vd.ltoreq.Vb.ltoreq.Vd as described above. The total amount of
the filtrate (provided that an amount of the dialysate is deducted
in the case of the dialysis device as the concentration element) is
not necessarily substantially the same as the total amount of the
supplied fluid replacement, these amounts may be different as far
as no problem occurs during the treatment. From such viewpoint, it
is generally sufficient to keep a relationship of for example
0.8.times.total amount of filtrate (provided that an amount of the
dialysate is deducted in the case of the dialysis device as the
concentration element).ltoreq.total amount of supplied fluid
replacement.ltoreq.1.2.times.total amount of filtrate (provided
that an amount of the dialysate is deducted in the case of the
dialysis device as the concentration element). Since a certain time
is required for the fluid replacement to be discharged after
passing the cooled object, the pumps (5) and (7) of course do not
have to be started simultaneously with the operation start of the
pump (1). It is noted that during a practical treatment or
procedure, the supplied fluid replacement may be discharged as
urine, which is included by the total amount of the filtrate in the
present specification. That is, the urine is regarded to be the
filtrate and the above relationship is considered (provided that a
rate of the urine is not included in the filtrate rate Vb).
In the shown embodiment of the apparatus, the blood pump (5) has a
function to withdraw the diluted blood from the body (17), a
function to supply the diluted blood to the concentration element
(13) so as to allow the concentration of the diluted blood and a
function to return the concentrated blood to the body (17)
thereafter. It is obvious for those skilled in the art that these
functions may also be achieved by separate pumps while providing
inbetween buffers (or reservoirs)
In the blood concentration unit of the apparatus of the present
invention may include the drip chamber (12) for the removal of
bubbles and the anticoagulant supply element (18), for example a
heparin supply device. It is noted that the anticoagulant (for
example, heparin, fusan or the like) may supplied at any suitable
position in the apparatus of the present invention. In the shown
embodiment, the heparin supply device (18) is located in the blood
concentration unit, and the supplied heparin does not substantially
transfer to the filtrate even though it passes through the blood
concentration element (13) (namely, remaining in the concentrated
blood).
The apparatus of the present invention comprises the blood supply
unit which adjusts the temperature of the concentrated blood which
may be at a higher or lower temperature to around a normal body
temperature, and supplies such blood into a blood vessel (vein).
Concretely, the unit comprises a heat exchanger for warming/cooling
(6) which may be able to adjust the blood to for example around
37.degree. C. and supply it to usually a vein at a position which
is closer to the heart. In the concrete, upon using the apparatus
according to the present invention, the concentrated blood passes
the heat exchanger (6) through a conduit which is connected to an
blood outlet of the blood concentration device (13), and injected
into the vein through the catheter (15). In this case, there may be
provided a protamine supply pump (70), a drip chamber for bubble
removal (16) and a bubble detector (46).
In a preferable embodiment of the present invention, a
supply/removal (dehydration) control mechanism (19) is provided
which automatically controls each of the flow rate of the supplied
fluid replacement Vd, the flow rate of the withdrawn diluted blood,
and the flow rate of the filtrate Vb so as to keep a body fluid
amount as desired based on the balance of the flow rates. When the
urine is discharged, the control of the balance may be carried out
while considering an amount of the urine. When the supply/removal
control mechanism (19) is used in the apparatus of the present
invention, the flow rate of the supplied fluid replacement, the
flow rate of the withdrawn blood, and the flow rate of the filtrate
(thus, delivery rates of the pumps (1), (5) and (7), the last rate
including a rate of the dialysate) should have to be in controlled
conditions along with a purpose of the treatment in which the
apparatus is used. That is, the pumps (1) and (5) and optionally
the pump (7) should be cooperated as shown with the broken lines
such that Vb and Vd satisfy the ranges for them as described above,
the relationship between Vb and Vd as described above and the
relationship between the total amount of the filtrate (provided
that an amount of the dialysate is deducted in the case of the
dialysis device as the concentration element) and the total amount
of the supplied fluid replacement as described above. Such control
is well known to those skilled in the art and employed in an
operation of an artificial kidney. It is noted that in place of the
pump (7), other pump may be located on the concentrated blood side
of the blood concentration element (13) (i.e. downstream of the
concentration element).
For example, it is not necessarily required that the filtrate of
which amount corresponds to an amount of the supplied fluid
replacement is immediately discharged. Of course, it may be
possible so, but it is preferable that the fluid replacement is
held in the body for a certain period so as to achieve the purpose
of the treatment in which the selective temperature controlling
method is carried out, and then withdrawn gradually from the body
so as to avoid the excessive overhydration of the body fluid. Vb
and Vd are preferably controlled by the supply/removal control
mechanism (19) so as to achieve such purpose.
Alternatively, hematocrit values of the withdrawn diluted blood
and/or the concentrated blood are measured on line using a
non-contact type hematocrit measuring device, and the
supply/removal control mechanism (19) controls the flow rates of
the pumps (1), (5) and (7) based on the measurements of the
hematocrit values so as to keep the hematocrit value of the diluted
blood for example not smaller than 5% and/or to keep the hematocrit
value of the concentrated blood for example at least 40%.
The extracorporeal circulation apparatus shown in the drawings are
able to be used in the selective temperature controlling method for
example as described below which will be explained by an example of
the selective cooling:
Case 1
Fluid replacement is charged beforehand from a fluid replacement
tank (22) into the elements and the conduits in the apparatus.
First, an object (24) to which the selective cooling method is
applied, a predetermined temperature (T0) to which the object is
cooled depending on a treatment for the object, and operation
conditions such as a supplied fluid replacement rate, a withdrawn
diluted blood rate and so on are determined. Then, a heat exchanger
(3) is operated, and its adjusting temperature (T3) is set at for
example the predetermined temperature (T0). Upon this, the
adjusting temperature (T3) may be shifted a little from the
predetermined temperature (T0) considering the heat absorption or
heat loss after leaving the heat exchanger (3) until entering the
body (namely, .DELTA.T) as well as the temperature change after
entering the body until reaching the object.
Each catheter is inserted into the body, and the pump (1) is
operated and the fluid replacement is supplied from the fluid
replacement tank (8) to the heat exchanger (3), whereby the fluid
replacement temperature is adjusted to or near the predetermined
temperature (T0) and the fluid replacement is supplied into the
body. Simultaneously or a predetermined period later, the pump (5)
withdraws the diluted blood from the body, and the temperature
thereof (T1) is measured by the temperature sensor (20). The
diluted blood is supplied to the blood concentration element (13)
where the blood is separated by means of filtration. Upon
filtration, the dehydration (or water removal) pump (7) may be
optionally operated so as to help the blood concentration. The
blood concentrated by means of the filtration is passed through the
heat exchanger (6) so as to heat to a predetermined temperature and
then returned into the body through the catheter (15).
The above operation is carried out in the case where the measured
diluted blood temperature (T1) may be regarded to represent an
actual temperature of the region of the object, and thus the
different extent between T1 and the predetermined temperature of
the object region (T0), for example the difference .DELTA.Ta
(=T1-T0) is obtained. When .DELTA.Ta>0, it means that the object
has not been sufficiently cooled, and thus an operation to lower
the set temperature (T3) of the heat exchanger (3) is carried out,
which may be manually or automatically.
On the other hand, when .DELTA.Ta<0, it means that the object
has been excessively cooled, and an operation to raise the set
temperature (T3) of the heat exchanger (3) is carried out.
Thereafter, the diluted blood temperature is measured again, and
.DELTA.Ta is obtained similarly. Based on the obtained .DELTA.Ta,
the set temperature (T3) of the heat exchanger (3) is changed. The
time interval between the first calculation of .DELTA.Ta and the
second calculation of .DELTA.Ta is not particularly limited, but
when it is excessively long, the diluted blood temperature (T1) is
likely to hunt, so that the interval is preferably short. It is of
course possible that the diluted blood temperature (T1) is
continuously measured, so that the set temperature (T3) of the heat
exchanger (3) is considered while considering a characteristic of
the temperature difference .DELTA.Ta therefrom (such as an absolute
value of the temperature difference, a change rate with time of the
temperature difference or the like). The measurement and the change
of the set temperature (T3) of the heat exchanger (3) as described
above are repeated such that .DELTA.Ta becomes smaller whereby the
diluted blood temperature (T1) approaches the predetermined
temperature of the object (T0) and such temperature is kept. It is
noted that when .DELTA.Ta is substantially zero, the set
temperature (T3) of the heat exchanger (3) does not particularly
have to be changed.
Case 2
Although in Case 1, only the diluted blood temperature (T1) is
taken into account, the supplied fluid replacement temperature (T2)
is also considered in addition to the diluted blood temperature
(T1) in Case 2. In this case, the averaged temperature Tav of T1
and T2 (=(T1+T2)/2) may be regarded to indicate the actual
temperature of the object (T0), and this case is generally superior
to Case 1 wherein only T1 is considered in the estimation of the
object temperature. Similarly to Case 1 before, the different
extent between the averaged temperature (Tav) and the predetermined
temperature of the object region (T0), for example the difference
.DELTA.Tb (=(T1-T2)/2-T0) is obtained. The others are substantially
the same as those in Case 1. It is noted that T1 and T2 have the
same weight in the above so as to obtain the averaged value, but it
may be possible to change their weights. For example, it is
possible to use 1.5.times.T1 in place of T1, and 0.5.times.T2 in
place of T2. Particularly since T1 is affected by the object
temperature, it may be preferable that T2 is regarded to be
heavier.
When .DELTA.Tb>0, it means that the object has not been
sufficiently cooled, and thus an operation to lower the set
temperature (T3) of the heat exchanger (3) is carried out. On the
other hand, when .DELTA.Tb<0, it means that the object has been
excessively cooled, and an operation to raise the set temperature
(T3) of the heat exchanger (3) is carried out. Thereafter, the
measurement is repeated, and Tav and .DELTA.Tb are made approach
the predetermined temperature T0 and zero, respectively similarly
to Case 1, which conditions are kept.
Case 3
Temperature control of the heat exchanger (3) may be carried out in
various appropriate manners depending on the different extent, for
example the value of the difference .DELTA.Ta or .DELTA.Tb.
For example, when the difference .DELTA.Ta is positive in Case 1,
the adjust temperature of the heat exchanger (3) is operated so as
to lower the diluted blood temperature (T1). When the difference
.DELTA.Ta is negative, the opposite operation is carried out. Upon
these operations, it is preferable to consider a static
characteristic and/or a dynamic characteristic of the difference
.DELTA.Ta.
For example, when the difference .DELTA.Tb is positive in Case 2,
the adjust temperature of the heat exchanger (3) is operated so as
to lower the supplied fluid replacement temperature (T2). Upon this
operation, considering that the difference .DELTA.Tb desirably
becomes zero, T2 is calculated from the predetermined temperature
(T0) and the measured diluted blood temperature through an
equation: T2=2T0-T1. The calculated T2 is used as the set
temperature of the heat exchanger (3). In other embodiment, the set
temperature (T3) of the heat exchanger (3) is determined based on
the calculated T2 through the calibration curves or the above
equation (I) under consideration of the heat exchange with the
surrounding from the heat exchanger (3) to the temperature
measurement position of the supplied fluid replacement. As seen
from the equation, T3 varies depending on the supply rate of the
fluid replacement (v). In the treatment which is carried out using
the selective cooling method, v is usually not an arbitrary value,
but has been determined beforehand within an acceptable range (for
example v is in an range within which no damage is given to an
inner wall of a blood vessel). Therefore, the acceptable value of v
is preferentially determined, and then other parameter values are
determined depending on the apparatus to be used so that T3 is
finally determined.
Upon using the apparatus of the present invention, the fluid
replacement flows from its container (8) through the supply pump
(1) to the heat exchanger for the fluid replacement temperature
adjustment (3) where its temperature is adjusted, and then injected
by means of the catheter (10) into the body through a blood vessel,
usually an artery which leads to the object to which the selective
temperature adjusting method is applied. The catheter is inserted
into the blood vessel (vein) which leads to the object to which the
selective temperature adjusting method is applied, and the position
at which the catheter is inserted is not necessarily near the
object. It may be possible to employ a method such as a so-called
Seldinger's method with which a catheter is transdermally inserted
into for example a femoral artery up to a brain followed by
supplying the fluid replacement.
In such case, it is preferable not to locate the supplied fluid
replacement temperature sensor (4) outside the body but to locate
it at a tip or vicinity thereof of a leading end of the catheter
(10) upon the insertion thereof, so that a temperature of the
supplied fluid replacement (T2') may be measured at a position
which is closer to the object region (i.e. at a more distal
position). As a result, T2' is used in place of T2 which is used
for the estimation of the temperature of the object region in Case
2 as the above. Similarly, as to the withdrawal of the diluted
blood from the object region, the leading end of the catheter is
inserted as close to the object region as possible and the
temperature sensor is located at a tip or vicinity thereof of a
leading end of the catheter, so that a temperature of the diluted
blood (T1') can be measured at a position which is closer to the
object region.
Therefore, by locating the temperature sensor at the tip of the
leading end of the inserted catheter, accuracy of the estimation of
the object region temperature is further improved, so that the
selective temperature controlling method is effectively carried
out. That is, T1' is used in place of T1 in Case 1, and T1' and T2'
are used in place of T1 and T2 in Case 2, so that the temperature
estimation of the object region is further reliable. It is noted
that an embodiment involving T1' and T2' is schematically shown in
FIG. 5.
In the embodiment shown in FIG. 1, a blood pressure measuring
element (48) for the withdrawn diluted blood pressure, is located
before the pump (5), and a drip chamber (52) and a cramp (54) are
located downstream of the fluid replacement tank (22).
In a preferable embodiment, the apparatus of the present invention
further comprises an artificial lung which oxygenates the diluted
blood, the fluid replacement, the autologous blood and/or the
transfusion blood.
In FIG. 2, the apparatus of the present invention which includes a
configuration which oxygenates a portion of the diluted blood
withdrawn from the body is schematically shown (only a portion of
such configuration is shown and the other portions are
substantially the same as those in FIG. 1 except that
configuration). In the shown embodiment, a portion of the diluted
blood drawn from the body is divided before the diluted blood
supplied to the concentration element (13) by the pump (26), and
such portion is supplied to the artificial lung (28) through a
liquid empty detector (58) and a drip chamber (60). Oxygen is
supplied to the artificial lung (28). The diluted blood leaving the
artificial lung (28) is merged to the fluid replacement which is
freshly supplied, followed by passing through the heat exchanger
(3) and thereafter to the body (17).
In the embodiment shown in FIG. 3, autologous blood beforehand
obtained from a patient to be treated and/or transfusion blood (31)
is supplied to the body through the artificial lung (28). Similarly
to FIG. 2, FIG. 3 shows only a portion which is different from that
of FIG. 1. The autologous blood or the transfusion blood is passed
to the artificial lung (28) through a liquid empty detector (62)
and a drip chamber (64) by a pump (30), and thereafter merged to
the fluid replacement which is freshly supplied, followed by
passing through the heat exchanger (3) and thereafter to the body
(17).
In the embodiment shown in FIG. 4, the fluid replacement which is
to be supplied to the body is supplied to the artificial lung (28)
after it leaves the heat exchanger (3), followed by passing to the
body. It is noted that the configurations other than that shown in
FIG. 4 are substantially the same as those in FIG. 1.
In addition to or in place of the artificial lung as described
above, it is possible that oxygen gas is supplied to a drip chamber
(9) which is located before the body after the heat exchanger (3)
in a supply line for the fluid replacement, so that oxygen is
bubbled in the fluid replacement (optionally including the
autologous blood or the transfusion blood) passing through the drip
chamber so as to oxygenate it.
It is noted that FIG. 5 also shows an embodiment in which the
conduit exiting the heat exchanger or warming/cooling device (6) is
connected to the fluid supply conduit. In such embodiment, when the
selected object has been cooled to the predetermined temperature,
the required treatment has been carried out, and then the object is
returned to its original temperature (namely, upon the temperature
recovery), an operation is carried out such that at least a portion
of the concentrated and recovered blood is supplied to the object
together with the fluid replacement. The temperature recovery is
substantially the same as warming the selected object using the
apparatus according to the present invention, and thus the
temperature recovery operation may be carried out by the selective
warming method using the apparatus of the present invention. On the
other hand, when the selected object has been warmed to a
predetermined temperature, the required treatment has been carried
out, and then the object is returned to its original temperature
(namely, upon the temperature recovery), the temperature recovery
operation may be carried out by the selective cooling method using
the apparatus of the present invention.
Upon the temperature recovery, when the object temperature is
raised, the metabolism function of the object is accelerated so
that supply of oxygen may be desirable. In such case, it is
preferable to replace at least a portion of the fluid replacement
which is to be supplied to the body with blood, and supply them to
the object. In that case, a bypass line 100 (shown with the broken
line) is provided as shown in FIG. 5 so that at least a portion of
the concentrated blood is divided after the temperature adjustment,
and supplied together with the fluid replacement. Usually, when the
object temperature is increased, the metabolism is accelerated, so
that the object requires a more amount of oxygen. Thus, it is
preferable to gradually increase an amount of the concentrated
blood to be divided while an amount of the fluid replacement is
gradually reduced. It may be preferable that only the blood is
supplied finally and the supply of the fluid replacement is
stopped. In such case, it is preferable that the blood is
oxygenated by for example the artificial lung. Upon such
temperature recovery, the object temperature is estimated based on
the measured diluted blood temperature (T1, which is a drawn blood
temperature when the supply of the fluid replacement is stopped)
and the measured supplied fluid replacement temperature (T2, which
may be a supplied blood temperature when the supply of the fluid
replacement is stopped) while the supplied fluid replacement
temperature and the divided recovered blood temperature are
controlled. It is noted that upon the provision of the bypass line
100, it is preferable that a valve or the like is located so as to
supply a total amount or a portion of the concentrated and
recovered blood to the fluid replacement supply conduit, whereby a
volume of the blood to be returned to the body directly (i.e. blood
return side) and a volume of the blood to be supplied to the object
together with the fluid replacement (i.e. fluid replacement side)
are appropriately divided. In addition, it is possible that for
example a Y-shaped coupler is located beforehand in a conduit of
the fluid replacement, and the catheter (15) is pulled out and
connected to the Y-shaped coupler so that the blood return conduit
is directly connected to the conduit of the fluid replacement,
whereby a total amount of the blood is supplied to the fluid
replacement side. Further, the catheter (15) pulled out may be
inserted into the drip chamber (9) for the fluid replacement.
Effects of the Invention
By using any of the embodiments of the apparatus according to the
present invention, the object to which the selective temperature
controlling method is applied is able to be kept in a desired
temperature condition with an improved accuracy. Particularly, when
the position for the temperature measurement is close to the
object, namely the temperature measurement is carried out most
closely to the body, the accuracy is further improved. Especially,
when the temperature sensor is located at around the leading tip of
the catheter which is inserted into the blood vessel, the accuracy
becomes remarkable. Thus, the advantages of the selective
temperature controlling method can be further remarkable.
The apparatus of the present invention may be used for a case in
which the selective temperature controlling method is applied upon
any of surgical operations. For example, by cooling an affected
part in a brain, a breast, an abdominal part, an extremity or the
like to a predetermined temperature accurately by means of the
fluid replacement, activity of for example the organ is suppressed
and a progress of a trauma (for example, damage of a tissue due to
ischemia) is avoided, operation safety is increased by forming a
hypotension condition (for example, a low irrigation condition),
and reduction of an amount of used heparin as well as an amount of
the transfusion blood, so that an operation becomes possible
without a risk of infection due to the blood transfusion.
In addition, using the apparatus of the present invention, the
selective temperature controlling method as the selective cooling
method is used not only during an operation but may be employed as
a part of a method to control a condition, and particularly control
a low active condition of a patient. That is, by accurately keeping
an affected part in a diluted blood condition at a desired
temperature (which includes keeping at a body temperature (normal
temperature)), the progress of illness may be delayed or
prevented.
For example, when a part of the body is wished to be cooled to a
certain extent, for example to a temperature within a range of
about 34 to 15.degree. C. and preferably rapidly, but the other
parts are not wished to be cooled to such low temperature (for
example not wished to be lower than 28.degree. C.), only that part
can be cooled rapidly and accurately by using the apparatus of the
present invention. As an example, there is a case in which before a
treatment of a brain bruise, only a brain is to be cooled rapidly
so as to delay (or reduce) swelling of the brain, but the other
parts are not to be cooled.
Particularly, the apparatus of the present invention cools only a
part of the body and the other parts are not so cooled, and only
the part of the body is able to be kept at a very low temperature
accurately while the body as a whole is kept at a relatively higher
temperature (or a normal temperature) by adjusting the temperature
and the supply rate of the fluid replacement. This means that only
the brain can be cooled rapidly during a treatment of brain
contusion because of for example a traffic accident, which is very
effective to a craniotomy operation. In addition, since the
apparatus of the present invention cools only a part of the body
while the other parts are cooled not so much, no side effect
occurs, so that the part of the body may be kept at the low
temperature for an extended period.
Further, when the fluid replacement is supplied using the apparatus
of the present invention, a part of the body is temperature
controlled while the blood is diluted. In the case of the selective
cooling method, since the metabolism of that part is suppressed by
cooling (thus, oxygen consumption of the cooled tissue is reduced,
namely the low active condition is kept), it is sufficient that
only the diluted blood is supplied to such tissue. Therefore, upon
the operation of such part, only the diluted blood flows the part,
so that an amount of hemorrhage is greatly reduced.
The present invention provides the apparatus which is used for the
condition control as described above, namely the condition control
apparatus. In the present specification, the condition control is
used to mean to keep a limited part or a whole body of a patient at
a predetermined temperature, for example to keep in a low active
condition at a low temperature, or to keep in a condition at a
warmed temperature such that a low body temperature condition due
to hypothermia is improved or malignant cells are killed, whereby
controlling so as to delay or prevent progress of the illness.
Particularly, in the latter condition control, accurate temperature
keeping of the object is very important (especially, an excessive
high temperature should be avoided) from a viewpoint of the
protection of the normal cells, and in this sense, the apparatus of
the present invention which is able to keep the object at the
predetermined temperature accurately is very effective.
As explained at the beginning, the apparatus of the present
invention is applicable to the treatment for an animal including a
human. The conditions (including the numerical values) and the
embodiment disclosed in the present specification are generally
used for such a treatment, and more appropriate embodiments may be
selected by repeating experiments depending on concrete cases.
Upon such selection, as parameters with which the apparatus of the
present invention is controlled, data of a patient (such as a body
weight, a hematocrit value, an object to be treated and the like),
data of cooling and warming which has been collected up to now
(such as a kind and a temperature of a fluid replacement, a
supplied fluid replacement rate, a region to be cooled and its
temperature change with time, a withdrawn diluted blood rate, a
temperature change of the other parts with time and the like), a
kind of treatment (such as a part to be treated, a treatment
method, a treatment time and the like), and data of a filtration
device (such as a kind of filter medium, a filtration pressure, a
filtration rate and the like). Those various data are collected
upon the experiments, which are then numerically analyzed
(regressed), so that they can be used for the practical
treatment.
Further, when the artificial lung is provided in the extracorporeal
circulation apparatus of the present invention, there is provided
an advantage in that an operation time is extended by the
oxygenation of the fluid replacement.
* * * * *